This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Friedman, H.
Right arrow Articles by Klein, T. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Friedman, H.
Right arrow Articles by Klein, T. W.

 Previous Article  |  Next Article 

Clinical Microbiology Reviews, April 2003, p. 209-219, Vol. 16, No. 2
0893-8512/03/$08.00+0     DOI: 10.1128/CMR.16.2.209-219.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Microbial Infections, Immunomodulation, and Drugs of Abuse

Herman Friedman,* Catherine Newton, and Thomas W. Klein

Department of Medical Microbiology and Immunology, College of Medicine, University of South Florida, Tampa, Florida 33612

SUMMARY
INTRODUCTION AND HISTORICAL BACKGROUND
OPIATE EFFECTS ON IMMUNITY AND SUSCEPTIBILITY TO INFECTION
MARIJUANA-INDUCED ENHANCEMENT OF SUSCEPTIBILITY TO INFECTION
COCAINE AND INFECTIONS
NICOTINE EFFECTS ON RESISTANCE TO INFECTIONS
ALCOHOL MODULATION OF RESISTANCE TO INFECTION
DISCUSSION
ACKNOWLEDGMENTS
REFERENCES

arrow
SUMMARY
 
The use of recreational drugs of abuse has generated serious health concerns. There is a long-recognized relationship between addictive drugs and increased levels of infections. Studies of the mechanisms of actions of these drugs became more urgent with the advent of AIDS and its correlation with abused substances. The nature and mechanisms of immunomodulation by marijuana, opiates, cocaine, nicotine, and alcohol are described in this review. Recent studies of the effects of opiates or marijuana on the immune system have demonstrated that they are receptor mediated, occurring both directly via specific receptors on immune cells and indirectly through similar receptors on cells of the nervous system. Findings are also discussed that demonstrate that cocaine and nicotine have similar immunomodulatory effects, which are also apparently receptor mediated. Finally, the nature and mechanisms of immunomodulation by alcohol are described. Although no specific alcohol receptors have been identified, it is widely recognized that alcohol enhances susceptibility to opportunistic microbes. The review covers recent studies of the effects of these drugs on immunity and on increased susceptibility to infectious diseases, including AIDS.


arrow
INTRODUCTION AND HISTORICAL BACKGROUND
 
The recreational use of legal and illegal drugs of abuse in this country and abroad has aroused serious concerns about the consequences of these drugs on immunity. Marijuana, cocaine, heroin, and other opiates are widely used illegal drugs. There have been numerous clinical reports on the association between infectious diseases and use of illegal drugs. In addition, legal substances such as alcohol and tobacco have been linked to excessive and addictive use and have been correlated with major health problems. Heavy smokers and/or alcoholics are often hospitalized with infectious diseases. Experimental studies using drugs of abuse support the clinical observations that these substances are associated with immunomodulation.

Studies concerning the effects of addictive drugs on immunity became even more urgent with the onset of the worldwide epidemic of AIDS. AIDS is caused by human immunodeficiency virus (HIV) and results in a collapse of the immune system, making an individual highly susceptible to opportunistic microorganisms (77, 130, 150). Drugs of abuse have been suggested as possible cofactors, resulting in a more rapid progression of disease (58, 63, 69, 212). Approximately one-third of all AIDS patients in the United States are intravenous drug users (IVDUs), and contaminated needles or equipment often spreads HIV (57). AIDS patients also often use other drugs such as marijuana, alcohol, and nicotine, which some investigators think are immunosuppressive (13, 59, 106, 216). Thus, there is concern that abused drugs are serving as cofactors in AIDS progression and in alteration of susceptibility to other infectious diseases (63, 73, 124, 161, 164).


arrow
OPIATE EFFECTS ON IMMUNITY AND SUSCEPTIBILITY TO INFECTION
 
Opiates compose a collection of drugs derived from the poppy Papaver somniferum (199) which include opium, morphine, and heroin. An excellent review of the historical use of opiates has been written by Risdahl et al. (190). It is clear from this review that opiates have had a great impact throughout history on mankind both from use and from the wars over the control of opium. Opium was derived from the Greek word meaning "of sap" or "juice", because the drug is obtained from the juice of the poppy plant. Relics from the Stone Age, pre-dating recorded history, show widespread poppy cultivation. Over time, the addictive nature of opium was also recognized. First morphine (in the early 1800s) and then codeine, heroin, and other opium alkaloids (in the late 1800s) were synthesized from opium with claims of being the cure of opium addiction (91).

During the late 1800s and early 1900s, many medical practitioners began to recognize infections as serious complications of opiate addiction (28, 105, 165, 260). The list of infections associated with opiates continued to increase during the 1900s (89, 90). Also, experimental evidence began to accumulate during this time demonstrating the detrimental effects of opiates on immunity in humans and animals (90, 115, 116, 123, 187). For example, Cantacuzene demonstrated in the late 1890s that morphine-treated guinea pigs had altered phagocytosis and leukocyte trafficking (36). Studies of drug addicts in the early 1970s further demonstrated a connection between drug use and infectious diseases (117, 185). It is now recognized that IVDUs face many complications from the use of opiates (243). Pulmonary infections, caused by Mycobacterium, Staphylococcus, Streptococcus, Haemophilus, and other bacteria, are among the most common diagnoses of opiate abusers (190). Other serious diseases caused by microbial pathogens in IVDUs are AIDS (HIV), endocarditis (Staphylococcus, Enterococcus, Pseudomonas, Klebsiella, Serratia, and Candida), abscesses and cellulitis (Staphylococcus, Streptococcus, Haemophilus, Enterobacter, Pseudomonas, Klebsiella, Clostridium, Candida, and others), hepatitis A, B, and C (hepatitis A, B, and C viruses), sexually transmitted diseases, and skeletal infections (Staphylococcus and Pseudomonas) (77, 188, 190).

A large percentage of infections among IVDUs are related to the methods of injection and life-style practices, which increase their exposure to microbial pathogens (57). Recent reports continue to discuss the problem of contaminated heroin or drug paraphernalia and infections (15, 47). Numerous investigators, however, have proposed that increased exposure is not the only factor that enhances microbial infections. They hypothesize that opiates cause immunosuppression and therefore serve as cofactors for microbial infections. These studies have been previously reviewed (59, 139). They have been expanded on by the advent of the AIDS epidemic in the 1980s (30, 176). AIDS and its corresponding decreased host immunity were, and still are, principal players in opportunistic infectious diseases in IVDUs (63, 76, 124, 150). Several studies support that intravenous use of opiates influences the outcome of HIV infection (16, 58, 63). Heroin addicts have been observed to have an increased risk of acquiring HIV (16, 227), and at one time half of IVDUs from certain areas of the United States were infected with HIV (103). Moreover, mortality rates from infectious diseases among HIV-infected IVDUs decrease when drug use was discontinued, and this abatement correlated with a decrease in the rate of progression to AIDS (256). Therefore, a correlation between the use of opiates, increased susceptibility to infection, and depressed immunity does indeed exist. Whether this correlation is due, however, to increased exposure to infectious pathogens through risky behaviors, to immunosuppressive effects of opiates, or to a combination of these two is uncertain at this time.

Experimental studies to investigate the effect of opioids on immune responses and on microbial pathogens have extended the earlier clinical correlative observations and animal studies (Tables 1 and 2). Several good reviews of these studies have been previously published (59, 139, 188, 190). Several opiate receptors have been identified on cells of the nervous system, with µ-, {kappa}-, and {delta}-receptors and their subtypes being the most predominant and being referred to as classical receptors (2). The classical receptors are G-protein coupled seven-transmembrane receptors (186). Opiates have been linked to modulations of host resistance to bacterial, protozoan, viral, and fungal infections, using animal models, cell lines, and primary cells. Opiates appear to affect the immune response directly through opioid receptors on immune cells and indirectly via the receptors on neuronal cells. The µ-, {kappa}-, and {delta}-opioid receptors as well as nonclassical opioid-like receptors have been demonstrated on immune cells, suggesting possible mechanisms for the direct actions of opiates on immune cells (139). In vitro studies of immune cells have demonstrated receptor-mediated reduced phagocytosis (235), chemotaxis (71), and cytokine and chemokine production (4, 22, 39, 179).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Effects of opiates on immune functions in vivo and in vitro


View this table:
[in this window]
[in a new window]
  		TABLE 2. Opiates and microbial pathogens

While opiates directly modulate host immunity, their effects on physiological function of nonspecific host mechanisms are thought to also alter immune responses and play an important role in increased susceptibility to infection. These effects are proposed to act through the central nervous system (CNS) and the hypothalamus-pituitary-adrenal (HPA) axis. Opiates are known to alter the release of HPA hormones (corticotrophin-releasing hormone and adrenocorticotrophic hormone) (5), which, in turn, alter glucocorticoids (cortisol and corticosterone), the end-effectors of the HPA axis. The glucocorticoids play an important role in decreasing and regulating cellular immune responses (29). Studies have shown that morphine treatments suppress immune parameters in mice through the HPA axis (31, 64, 183, 200, 201). In addition to these corticoids, immunosuppression via the autonomic nervous system has been observed (144, 257). Shavit et al. observed that natural killer (NK) activity in rats was suppressed following morphine injection into the lateral ventricle of the brain via opioid receptors (206, 207). The central opioid pathways were involved in immunosuppression of lymphocyte proliferation (78, 82, 126). Receptor-mediated increase in the production of transforming growth factor ß, an immunosuppressive cytokine, is another possible indirect method by which opiates suppress immunity (38). Thus, it appears that immunosuppression occurs through direct and indirect mechanism involving receptors on immune cells and the CNS.


arrow
MARIJUANA-INDUCED ENHANCEMENT OF SUSCEPTIBILITY TO INFECTION
 
Marijuana is the common name for Cannabis sativa, a plant that has long been known for its "medicinal" and recreational properties and for its fiber (hemp). Chemical extracts of marijuana contain over 400 compounds and more than 60 cannabinoids. Cannabinoids, especially the major psychoactive component {Delta}9-tetrahydrocannabinol (THC), exert immunomodulatory effects that alter normal functions of T and B lymphocytes, NK cells, and macrophages in human and animals. These modulations have been observed during both in vivo and in vitro cannabinoid treatment (Table 3). The molecular and cellular mechanisms for these effects are not fully defined; however, it appears that receptor as well as nonreceptor mechanisms are involved (106). Like opiate receptors, cannabinoid receptors (CBRs) are G-protein-coupled seven-transmembrane receptors of which two types have been identified, CB1 and CB2 (85, 86, 108, 134, 151, 174). CB1 receptors are associated with the brain and certain peripheral tissues and are responsible for behavioral effect of THC, while CB2 receptors are located in the periphery, especially on immune cells (86, 108, 174). The discovery of CBR has led to the identification of a class of endogenous compounds that bind to these receptors, called endocannabinoids, although the majority of the compounds are eicosanoids (53, 138, 142, 261). The broad spectrum of action of THC on immune functions is thought to result in decreased host resistance to bacterial and viral infections as observed in various experimental animal models (Table 4).


View this table:
[in this window]
[in a new window]
  		TABLE 3. Effects of THC and other cannabinoids on immune functions in vivo and in vitro


View this table:
[in this window]
[in a new window]
  		TABLE 4. Effects of cannabinoids on resistance to infections

Studies in the early 1970s using human peripheral blood mononuclear cells (PBMCs) from marijuana smokers showed a tendency for heavy use to result in suppression of lymphocyte proliferation in culture as well as alterations in PBMCs immune cell subsets (154). Serum immunoglobulin (Ig) levels were also modulated by marijuana use, with IgG protein levels decreasing and IgE protein levels increasing. Animal studies started in earnest with the isolation and synthesis of THC by Mechoulam et al. (143), when it became possible to inject THC into animals or treat human and animal cells in vitro. Various groups have observed both in vivo and in vitro that THC suppresses immune functions (Table 3). These functions vary from lymphocyte proliferation and antibody production to cytotoxic activity (Table 3). Other studies have demonstrated that THC enhances certain functions (Table 3). B-cell proliferation increased in the presence of THC at nanomolar concentrations (51), and the production of the chemokines MIP1{alpha} and interleukin-8 (IL-8); increased at micromolar concentrations (223). The latter group also observed decreases in the levels of other cytokine after THC treatment (223). Therefore, the data that have accumulated over the past three decades indicate that THC and cannabinoids are immunomodulatory.

One of the important risk factors of marijuana use is its suppression of host resistance to infections (99). This aspect has been studied in both humans and animals, and the results have suggested that cannabinoids have a moderating effect on various infection paradigms and that at least some of the effects involve CBRs (Table 4) (33, 112). A correlation between marijuana smoking and herpesvirus infection was observed to increase the risk of mortality in HIV positive marijuana smokers (211). Furthermore, alveolar macrophages from marijuana smokers were found to be deficient in several functional properties including phagocytosis and bactericidal activity (14). Experimental animal studies have also suggested that THC treatment causes increased susceptibility to various infectious agents (Table 4). Disease progression and mortality in different animal models were increased on infection with herpes simplex virus (HSV) and Friend leukemia virus (FLV) (35, 147, 222) and with bacterial pathogens such as Listeria, Treponema, and Staphylococcus (87, 149, 170).

These studies leave major gaps in our understanding of the cellular and molecular mechanisms mediating these effects on immunity and resistance. Immune cells have been demonstrated to express CBR; therefore, it is likely that at least a portion of the cannabinoid-induced modulations of the immune cells are directly mediated via their own CBRs (79, 119). The host immunity, however, involves many cell types, both immune and nonimmune, as well as chemical factors such as cytokines and chemokines and hormones of the HPA axis. Thus, there are numerous cellular and molecular mechanisms where THC could be exerting its effects as demonstrated by our Legionella pneumophila infection studies. In our studies, THC pretreatment of mice infected with THC affects both innate immunity and the development of the adaptive (cell-mediated) immune response. Initially, we reported that mice receiving a THC injection 1 day before and 1 day after a sublethal L. pneumophila infection died of septic shock resulting from a detrimental production of high levels of proinflammatory cytokines (111). Induction of tumor necrosis factor alpha (TNF-{alpha}) has since been confirmed, most recently in CB2-transfected HL60 cells stimulated with the cannabinoid agonist CP55,940 (52). We further observed that a single injection of THC 18 h prior to infection inhibited the development of Th1 immunity in mice (163), which involved both CB1 and CB2 receptors and suppression of Th1 development by inhibiting the production of gamma interferon and IL-12 and reducing the amount of IL-12Rß2 mRNA (112). This THC-induced shift away from a Th1 response has also been observed in other models involving THC treatment and tumor immunity (268), endotoxemic mice (215), and NK cell activity (133). These studies suggest that cannabinoids have the ability to bias the developing immune response from Th1 (cell-mediated) toward Th2 (antibody-mediated) immunity. Interestingly, Th shifts have also been observed toward Th2 following treatment with morphine (193) and toward Th1 following treatment with norepinephrine (229). It is possible, therefore, that drugs used either recreationally or therapeutically might enhance or suppress infections by modulating Th activity in the host. Clearly, the full extent of these findings needs clarification.


arrow
COCAINE AND INFECTIONS
 
Cocaine is derived from the coca plant, Erthroxylon coca. Being an alkaloid, cocaine is water soluble and readily absorbed through mucous membranes of the body. It appears to function at least partially through the sigma1 ({sigma}1) receptor, a protein first proposed to be involved with morphine binding (122, 135, 137, 205, 228). The {sigma}1 receptors are distributed throughout the brain and periphery of the body (137), similar to the classical opiate and cannabinoid receptors.

A limited number of in vivo and in vitro studies have been done to examine cocaine-induced modulation of immune responses (Tables 5) and infections (Table 6). Much of the work with cocaine and infections has been centered on HIV and progression to AIDS (13). Epidemiologic studies on IVDUs and AIDS link abuse of cocaine, even more than other drugs, to increased incidence of HIV seroprevalence and progression of AIDS (7, 37, 42, 56). Cocaine increases HIV infection of human PBMCs in vitro (12, 177). Roth et al., using a model of human PBMCs implanted into severe combined immunodeficient (SCID) mice, demonstrated that cocaine treatments resulted in increased numbers of HIV-infected PBMCs and viral load, as well as a decreased CD4/CD8 ratio (192). These immunomodulations may be through receptors located in the periphery, as was demonstrated with cocaine-induced suppression of mitogen-stimulated lymphoproliferation (171). Therefore, while studies of the immunological impact of cocaine have started, there is much more research in this area to be done.


View this table:
[in this window]
[in a new window]
  		TABLE 5. Effects of cocaine on immune functions


View this table:
[in this window]
[in a new window]
  		TABLE 6. Effects of cocaine on resistance to infections


arrow
NICOTINE EFFECTS ON RESISTANCE TO INFECTIONS
 
Cigarette smoking is linked to community-acquired pneumonia and is considered one of the risk factors for respiratory infections (6, 89, 196). Cigarette smoke is composed of two components, the vapor phase and the particulate phase. The immunosuppressive effects of smoke and nicotine occur in the particulate portion, thus suggesting that the nicotine is at least partially responsible for the inhibitory effects on the immune responses (Table 7) (216, 217). Nicotine is a small organic alkaloid synthesized by tobacco plants and is recognized as the addictive component of cigarettes. While its lipophilic nature allows small amounts to cross directly through cell membranes, the primary biological effects are proving to be receptor mediated. Nicotine is an agonist for nicotinic acetylcholine receptors (nAChRs), which are present on cells of the CNS as well as other cells throughout the body including immune cells (80, 118). The neural nAChRs are upregulated in smokers (118, 264). Rapid progression of nicotine from cigarette smoke in the lungs to the brain increases dopamine transmission within the brain in the shell of the nucleus accumbens, a region essential for reward processing that has been associated with addictive properties of other drugs including opiates, alcohol, and THC (180, 236).


View this table:
[in this window]
[in a new window]
  		TABLE 7. Effects of nicotine and cigarette smoke on host resistance mechanisms in vivo and in vitro

Nicotine appears to affect the immune system through nAChRs on cells in CNS and on immune cells similar to opiates and cannabinoids. Nicotine induces glucocorticoids, through the HPA axis, that modify the immune system (29, 80, 216) as well as directly affecting immune cells (74, 75, 136, 167, 217). Nicotine was demonstrated to enhance the growth of L. pneumophila and cause a corresponding inhibition of IL-6, TNF-{alpha}, and IL-12 in a murine alveolar macrophage cell line through nAChRs (136). The substance also affects murine splenocyte production of Th1- and Th2-associated cytokines in a differential manner (74, 75). Chronic nicotine treatment of rats induces T-cell anergy, depletes intracellular IP3-sensitive Ca2+ stores, and inhibits the antibody-forming cell response and lymphocyte proliferation, which may prevent the animals from developing a protective immune response to microbial pathogens (66, 67, 101). In vitro treatments of PBMCs by nicotine and other extracts from cigarette were observed to inhibit cytokine production (167). Rodents exposed to cigarette smoke in inhalation chambers have increased susceptibilities to infections when challenge with aerosolized bacteria or viruses (217). Smoking among HIV-positive individuals has also been linked to increased numbers of infections (164, 213).

Thus, it is important to determine how nicotine, a legal addictive drug, increases or alters susceptibility to infectious diseases. Studies of this nature have begun with the apparent linking of the effects to nAChRs. However, much more information is needed to ascertain the nature and mechanism whereby nicotine influences the immune response and thus affects host resistance to infectious diseases.


arrow
ALCOHOL MODULATION OF RESISTANCE TO INFECTION
 
Alcohol abuse causes widespread health problems including decreased liver functions and increased incidences of infectious diseases (45). Alcoholics have long been recognized to be particularly susceptible to infections and to be at a greater risk of community-acquired pneumonias (1, 43, 88, 128, 157, 160, 196, 225). Moderate alcohol use (one beer, or one glass of wine, or one mixed drink per day), which may be beneficial to the immune system (159, 230), is not covered here.

Alcohol, unlike the previous drugs of abuse discussed, does not appear to involve receptor mediation. Studies during the last decade have demonstrated that alcohol has multiple effects on the host immune responsiveness to microbial pathogens (Tables 8 and 9). These effects are characterized by depletion of circulating lymphocyte populations and altered lymphoid organ architecture and immune functions (95, 152, 209, 230). In addition, alcohol suppresses the production of cytokines important in antimicrobial immunity, such as TNF-{alpha} secreted by mononuclear cells in vitro and/or in vivo, including alveolar macrophages from rats (114, 160) and rhesus macaques (226). The suppression of TNF-{alpha} is posttranscriptional and involves TNF-{alpha}-converting enzyme-mediated processing of TNF-{alpha} (114, 267). Furthermore, in human monocytes, alcohol inhibits lipopolysaccharide LPS-induced activation of NF-{kappa}B, a transcription factor for inflammatory cytokines (129). Of particular interest is the observation that alcohol use also decreases Th1 cytokine levels and responses (68, 230, 232, 246, 247) and increases Th2 cytokine levels (68, 248, 251), similar to the effect observed with THC (112, 163, 268) and morphine (193). Indeed, Peterson et al. reported that IL-12 therapy could attenuate the suppressed cell-mediated immunity in ethanol-consuming mice (175).


View this table:
[in this window]
[in a new window]
  		TABLE 8. Effects of alcohol on immune functions


View this table:
[in this window]
[in a new window]
  		TABLE 9. Effects of alcohol on resistance to infections

Rodents given alcohol orally show modulation in immune cell functions (Table 8) and infections (Table 9). Bermudez and Young showed that ethanol augments the intracellular survival of Mycobacterium avium complex and impairs macrophage responses to cytokines (26). Ethanol treatment increases the growth of L. pneumophila in nonpermissive macrophage cultures (263). Furthermore, studies by Jerrells and colleagues showed that immune cells from mice given alcohol and infected with intracellular bacteria (Salmonella or Listeria) had increased susceptibility to the bacteria (94-97, 197, 208).

Alcohol has also been connected to viral infections. The HSV-2 incidence is increased in women who abuse alcohol (44). Experimental studies indicate that alcohol inhibits Th1 responses generated to LP-BM5, a retrovirus that causes a murine AIDS-like syndrome (3, 248, 251, 252). Whether alcohol serves as a cofactor in AIDS is uncertain (54, 146). However, alcohol does exacerbate opportunistic infections in murine AIDS-like syndrome (3, 202) and opportunistic infections are correlated with the progression of AIDS. Hepatitis C virus infection has also been linked to chronic liver disease in alcoholics (92). Animal studies indicate that alcohol enhances liver damage by activating CD8 cells (93) and increasing apoptosis (65). Thus, the animal models and clinical studies imply that alcohol abuse is detrimental to the host and causes increase susceptibility to disease from microbial pathogens.


arrow
DISCUSSION
 
In recent years there have been more studies concerning the relationship between the use of addictive drugs of abuse and the increased incidence of susceptibility to infectious diseases, including AIDS. These studies have shown that drugs of abuse, including marijuana, cocaine, opiates, alcohol, and nicotine, alter not only neuropsychological and pathophysiological responses of individuals but also immune functions. Such studies support the earlier correlative observations that the use of these drugs is associated with enhanced susceptibility to infectious diseases.

The mechanisms by which abused drugs increase susceptibility to infections in humans as well as experimental animals have begun to be delineated. From the studies reviewed here, it appears that all five classes of drugs affect the immune system through both indirect and direct mechanisms. One indirect method is drug-induced stimulation of the HPA axis, which results in glucocorticoid production and regulation of the immune system. In addition, these abused substances have direct actions on immune cells that seem to be receptor mediated for all of the drugs except alcohol. Studies of receptor-mediated effects on immunity and infection have been performed in detail with opiates and to a lesser degree with cannabinoids and have just been started with nicotine. Another common mechanism of action among the five classes of these abused drugs is their effect on Th1/Th2 responses, either by inhibition of Th1- or elevation of Th2-associated cytokines.

The correlation between IVDUs and HIV infections has led many investigators to propose that the immunomodulation mediated by drugs is a major factor contributing to the progression of AIDS in IVDUs. While it is impossible to determine the cause-and-effect relationships from epidemiological studies, there is growing consensus among investigators of drugs of abuse that drug-induced immunomodulation is involved. Studies of immunosuppression by drugs of abuse are supporting increased susceptibility to opportunistic infectious pathogens by alteration of the immune response. However, there is still convincing evidence that the social practices connected with drug abuse also contribute to increase exposure to infectious pathogens. In the end, it logically seems that it will be a combination of increased exposure and drug-induced immunomodulation that contributes to increase susceptibility to infectious pathogens. A concerted enterprise, however, is essential to determine the mechanisms by which drugs compromise immune responses in general and in concert with immunosuppressive viruses.


arrow
ACKNOWLEDGMENTS
 
We acknowledge with gratitude the invaluable contributions of Susan Pross and Yoshimasa Yamamoto, Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, to studies of the effects of alcohol and nicotine on immunity.

Studies in our laboratories were supported by research grants from the U.S. Public Health Service (DA03646, DA10683, AI45169, and DA07245).


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, College of Medicine, University of South Florida, Tampa, FL 33612. Phone: (813) 974-3281. Fax: (813) 974-4151. E-mail: hfriedma{at}hsc.usf.edu. Back


arrow
REFERENCES
 
    1
  1. Adams, H. G., and C. Jordan. 1984. Infections in the alcoholic. Med. Clin. North Am. 68:179-200.[Medline]
    2. 2
  2. Adler, M. W., E. B. Geller, T. J. Rogers, E. E. Henderson, and T. K. Eisenstein. 1993. Opioids, receptors, and immunity. Adv. Exp. Med. Biol. 335:13-20.[Medline]
    3. 3
  3. Alak, J. I., M. Shahbazian, D. S. Huang, Y. Wang, H. Darban, E. M. Jenkins, and R. R. Watson. 1993. Alcohol and murine acquired immunodeficiency syndrome suppression of resistance to Cryptosporidium parvum infection during modulation of cytokine production. Alcohol Clin. Exp. Res. 17:539-544.[CrossRef][Medline]
    4. 4
  4. Alicea, C., S. Belkowski, T. K. Eisenstein, M. W. Adler, and T. J. Rogers. 1996. Inhibition of primary murine macrophage cytokine production in vitro following treatment with the kappa-opioid agonist U50,488H. J. Neuroimmunol. 64:83-90.[CrossRef][Medline]
    5. 5
  5. Allolio, B., H. M. Schulte, U. Deuss, D. Kallabis, E. Hamel, and W. Winkelman. 1987. Effect of oral morphine and naloxone on pituitary-adrenal response in man induced by human corticotropin-releasing hormone. Acta Endocrinol. (Copenhagen) 114:509-514.
    6. 6
  6. Almirall, J., I. Bolibar, X. Balanzo, and C. A. Gonzalez. 1999. Risk factors for community-acquired pneumonia in adults: a population-based case-control study. Eur. Respir. J. 13:349-355.[Abstract]
    7. 7
  7. Anthony, J. C., D. Vlahov, K. E. Nelson, S. Cohn, J. Astemborski, and L. Solomon. 1991. New evidence on intravenous cocaine use and the risk of infection with human immunodeficiency virus type 1. Am. J. Epidemiol. 134:1175-1189.[Abstract/Free Full Text]
    8. 8
  8. Ashfaq, M. K., E. S. Watson, and H. N. Elsohly. 1987. The effect of subacute marijuana smoke inhalation on experimentally induced dermonecrosis by S. aureus infection. Immunopharmacol. Immunotoxicol. 9:319-331.[Medline]
    9. 9
  9. Baczynsky, W. O. T., and A. M. Zimmerman. 1983. Effects of {Delta}9-tetrahydrocannabinol, cannabinol and cannabidiol on the immune system in mice. II. In vitro investigation using cultured mouse splenocytes. Pharmacologist 26:12-19.
    10. 10
  10. Baczynsky, W. O. T., and A. M. Zimmerman. 1983. Effects of {Delta}9-tetrahydrocannabinol, cannabinol, and cannabidiol on the immune system in mice. I. In vivo investigation of the primary and secondary immune response. Pharmacologist 26:1-11.
    11. 11
  11. Bagasra, O., and L. Forman. 1989. Functional analysis of lymphocytes subpopulations in experimental cocaine abuse. I. Dose-dependent activation of lymphocyte subsets. Clin. Exp. Immunol. 77:289-293.[Medline]
    12. 12
  12. Bagasra, O., and R. J. Pomerantz. 1993. Human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells in the presence of cocaine. J. Infect. Dis. 168:1157-1164.[Medline]
    13. 13
  13. Baldwin, G. C., M. D. Roth, and D. P. Tashkin. 1998. Acute and chronic effects of cocaine on the immune system and the possible link to AIDS. J. Neuroimmunol. 83:133-138.[CrossRef][Medline]
    14. 14
  14. Baldwin, G. C., D. P. Tashkin, D. M. Buckley, A. N. Park, S. M. Dubinett, and M. D. Roth. 1997. Marijuana and cocaine impair alveolar macrophage function and cytokine production. Am. J. Respir. Crit. Care Med. 156:1606-1613.[Abstract/Free Full Text]
    15. 15
  15. Bangsberg, D. R., J. I. Rosen, T. Aragon, A. Campbell, L. Weir, and F. Perdreau-Remington. 2002. Clostridial myonecrosis cluster among injection drug users: a molecular epidemiology investigation. Arch. Intern. Med. 162:517-522.[Abstract/Free Full Text]
    16. 16
  16. Battjes, R. J., C. G. Leukefeld, R. W. Pickens, and H. W. Haverkos. 1988. The acquired immunodeficiency syndrome and intravenous drug abuse. Bull. Narc. 40:21-34.[Medline]
    17. 17
  17. Bautista, A. P. 2001. Acute alcohol intoxication and endotoxemia desensitize HIV-1 gp120-induced CC-chemokine production by Kupffer cells. Life Sci. 68:1939-1949.[CrossRef][Medline]
    18. 18
  18. Bayer, B. M., S. Daussin, M. Hernandez, and L. Irvin. 1990. Morphine inhibition of lymphocyte activity is mediated by an opioid dependent mechanism. Neuropharmacology 29:369-374.[CrossRef][Medline]
    19. 19
  19. Bayer, B. M., M. R. Gastonguay, and M. C. Hernandez. 1992. Distinction between the in vitro and in vivo inhibitory effects of morphine on lymphocyte proliferation based on agonist sensitivity and naltrexone reversibility. Immunopharmacology 23:117-124.[CrossRef][Medline]
    20. 20
  20. Bayer, B. M., M. C. Hernandez, and X. Z. Ding. 1996. Tolerance and cross tolerance to the suppressive effects of cocaine and morphine on lymphocyte proliferation. Pharmacol. Biochem. Behav. 53:227-234.[CrossRef][Medline]
    21. 21
  21. Bayer, B. M., S. E. Mulroney, M. C. Hernandez, and X. Z. Ding. 1995. Acute infusions of cocaine result in time- and dose-dependent effects on lymphocyte responses and corticosterone secretion in rats. Immunopharmacology 29:19-28.[CrossRef][Medline]
    22. 22
  22. Belkowski, S. M., C. Alicea, T. K. Eisenstein, M. W. Adler, and T. J. Rogers. 1995. Inhibition of interleukin-1 and tumor necrosis factor-alpha synthesis following treatment of macrophages with the kappa opioid agonist U50,488H. J. Pharmacol. Exp. Ther. 273:1491-1496.[Abstract/Free Full Text]
    23. 23
  23. Berkeley, M. B., S. Daussin, M. C. Hernandez, and B. M. Bayer. 1994. In vitro effects of cocaine, lidocaine and monoamine uptake inhibitors on lymphocyte proliferative responses. Immunopharmacol. Immunotoxicol. 16:165-178.[Medline]
    24. 24
  24. Bermudez, L. E., M. Petrofsky, P. Kolonoski, and L. S. Young. 1992. An animal model of Mycobacterium avium complex disseminated infection after colonization of the intestinal tract. J. Infect. Dis. 165:75-79.[Medline]
    25. 25
  25. Bermudez, L. E., M. Wu, J. Martinelli, and L. S. Young. 1991. Ethanol affects release of TNF and GM-CSF and membrane expression of TNF receptors by human macrophages. Lymphokine Cytokine Res. 10:413-419.[Medline]
    26. 26
  26. Bermudez, L. E., and L. S. Young. 1991. Ethanol augments intracellular survival of Mycobacterium avium complex and impairs macrophage responses to cytokines. J. Infect. Dis. 163:1286-1292.[Medline]
    27. 27
  27. Bhargava, H. N., P. T. Thomas, S. Thorat, and R. V. House. 1994. Effects of morphine tolerance and abstinence on cellular immune function. Brain Res. 642:1-10.[CrossRef][Medline]
    28. 28
  28. Biggam, A. G. 1929. Malignant malaria associated with the administration of heroin intravenously. Trans. R. Soc. Trop. Med. Hyg. 23:147.[CrossRef]
    29. 29
  29. Boumpas, D. T., G. P. Chrousos, R. L. Wilder, T. R. Cupps, and J. E. Balow. 1993. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann. Intern. Med. 119:1198-1208.[Abstract/Free Full Text]
    30. 30
  30. Bryant, H. U., E. W. Bernton, and J. W. Holaday. 1987. Immunosuppressive effects of chronic morphine treatment in mice. Life Sci. 41:1731-1738.[CrossRef][Medline]
    31. 31
  31. Bryant, H. U., and R. E. Roudebush. 1990. Suppressive effects of morphine pellet implants on in vivo parameters of immune function. J. Pharmacol. Exp. Ther. 255:410-414.[Abstract/Free Full Text]
    32. 32
  32. Bussiere, J. L., M. W. Adler, T. J. Rogers, and T. K. Eisenstein. 1992. Differential effects of morphine and naltrexone on the antibody response in various mouse strains. Immunopharmacol. Immunotoxicol. 14:657-673.[Medline]
    33. 33
  33. Cabral, G., and D. Dove Pettit. 1998. Drugs and immunity: cannabinoids and their role in decreased resistance to infectious diseases. J. Neuroimmunol. 83:116-123.[CrossRef][Medline]
    34. 34
  34. Cabral, G. A., P. J. McNerney, and E. M. Mishkin. 1986. Delta-9-tetrahydrocannabinol enhances release of herpes simplex virus type 2. J. Gen. Virol. 67:2017-2022.[Abstract/Free Full Text]
    35. 35
  35. Cabral, G. A., E. M. Mishkin, F. Marciano-Cabral, P. Coleman, L. Harris, and A. E. Munson. 1986. Effect of {Delta}9-tetrahydrocannabinol on herpes simplex virus type 2 vaginal infection in the guinea pig. Proc. Soc. Exp. Biol. Med. 182:181-186.[CrossRef][Medline]
    36. 36
  36. Cantacuzene, J. 1898. Nouvelles recherches sur le mode de destruction des vibrions dans l'organisme. Ann. Inst. Pasteur 12:273.
    37. 37
  37. Chaisson, R. E., P. Bacchetti, D. Osmond, B. Brodie, M. A. Sande, and A. R. Moss. 1989. Cocaine use and HIV infection in intravenous drug users in San Francisco. JAMA 261:561-565.[Abstract/Free Full Text]
    38. 38
  38. Chao, C. C., S. Hu, T. W. Molitor, Y. Zhou, M. P. Murtaugh, M. Tsang, and P. K. Peterson. 1992. Morphine potentiates transforming growth factor-beta release from human peripheral blood mononuclear cell cultures. J. Pharmacol. Exp. Ther. 262:19-24.[Abstract/Free Full Text]
    39. 39
  39. Chao, C. C., T. W. Molitor, K. Close, S. Hu, and P. K. Peterson. 1993. Morphine inhibits the release of tumor necrosis factor in human peripheral blood mononuclear cell cultures. Int. J. Immunopharmacol. 15:447-453.[Medline]
    40. 40
  40. Chao, C. C., B. M. Sharp, C. Pomeroy, G. A. Filice, and P. K. Peterson. 1990. Lethality of morphine in mice infected with Toxoplasma gondii. J. Pharmacol. Exp. Ther. 252:605-609.[Abstract/Free Full Text]
    41. 41
  41. Chen, G. J., D. S. Huang, B. Watzl, and R. R. Watson. 1993. Ethanol modulation of tumor necrosis factor and gamma interferon production by murine splenocytes and macrophages. Life Sci. 52:1319-1326.[Medline]
    42. 42
  42. Chiasson, M. A., R. L. Stoneburner, D. S. Hildebrandt, W. E. Ewing, E. E. Telzak, and H. W. Jaffe. 1991. Heterosexual transmission of HIV-1 associated with the use of smokable freebase cocaine (crack). Aids 5:1121-1126.[Medline]
    43. 43
  43. Chomet, B., and B. M. Gach. 1967. Lobar pneumonia and alcoholism: an analysis of thirty-seven cases. Am. J. Med. Sci. 253:300-304.[Medline]
    44. 44
  44. Cook, R. L., N. K. Pollock, A. K. Rao, and D. B. Clark. 2002. Increased prevalence of herpes simplex virus type 2 among adolescent women with alcohol use disorders. J. Adolesc. Health 30:169-174.[CrossRef][Medline]
    45. 45
  45. Cook, R. T. 1998. Alcohol abuse, alcoholism, and damage to the immune system—a review. Alcohol Clin. Exp. Res. 22:1927-1942.[Medline]
    46. 46
  46. Daaka, Y., W. Zhu, H. Friedman, and T. W. Klein. 1997. Induction of IL-2 receptor {alpha} gene by {Delta}9-tetrahydrocannabinol is mediated by nuclear factor {kappa}B and CB1 cannabinoid receptor. DNA Cell Biol. 16:301-309.[Medline]
    47. 47
  47. Dancer, S. J., D. McNair, P. Finn, and A. B. Kolsto. 2002. Bacillus cereus cellulitis from contaminated heroin. J. Med. Microbiol. 51:278-281.[Abstract/Free Full Text]
    48. 48
  48. Darban, H., R. R. Watson, J. Alak, and N. Thomas. 1993. Cocaine facilitation of cryptosporidiosis by murine AIDS in male and female C57/BL/6 mice. Adv. Exp. Med. Biol. 335:143-151.[Medline]
    49. 49
  49. Delafuente, J. C., and C. L. DeVane. 1991. Immunologic effects of cocaine and related alkaloids. Immunopharmacol. Immunotoxicol. 13:11-23.[Medline]
    50. 50
  50. Derkinderen, P., C. Ledent, M. Parmentier, and J. A. Girault. 2001. Cannabinoids activate p38 mitogen-activated protein kinases through CB1 receptors in hippocampus. J. Neurochem. 77:957-960.[CrossRef][Medline]
    51. 51
  51. Derocq, J., M. Segui, J. Marchand, G. LeFur, and P. Casellas. 1995. Cannabinoids enhance human B-cell growth at low nanomolar concentrations. FEBS Lett. 369:177-182.[CrossRef][Medline]
    52. 52
  52. Derocq, J. M., O. Jbilo, M. Bouaboula, M. Segui, C. Clere, and P. Casellas. 2000. Genomic and functional changes induced by the activation of the peripheral cannabinoid receptor CB2 in the promyelocytic cells HL-60. Possible involvement of the CB2 receptor in cell differentiation. J. Biol. Chem. 275:15621-15628.[Abstract/Free Full Text]
    53. 53
  53. Devane, W. A., L. Hanus, A. Breuer, R. G. Pertwee, L. A. Stevenson, G. Griffin, D. Gibson, A. Mandelbaum, A. Etinger, and R. Mechoulam. 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946-1949.[Abstract/Free Full Text]
    54. 54
  54. Dingle, G. A., and T. P. Oei. 1997. Is alcohol a cofactor of HIV and AIDS? Evidence from immunological and behavioral studies. Psychol. Bull. 122:56-71.[CrossRef][Medline]
    55. 55
  55. Djeu, J. Y., M. Wang, and H. Friedman. 1991. Adverse effect of {Delta}9-tetrahydrocannabinol on human neutrophil function. Adv. Exp. Med. Biol. 288:57-62.[Medline]
    56. 56
  56. Doherty, M. C., R. S. Garfein, E. Monterroso, D. Brown, and D. Vlahov. 2000. Correlates of HIV infection among young adult short-term injection drug users. Aids 14:717-726.[CrossRef][Medline]
    57. 57
  57. Donahoe, R. M. 1990. Drug abuse and AIDS: causes for the connection. NIDA Res. Monogr. 96:181-191.[Medline]
    58. 58
  58. Donahoe, R. M., and A. Falek. 1988. Neuroimmunomodulation by opiates and other drugs of abuse: relationship to HIV infection and AIDS. Adv. Biochem. Psychopharmacol. 44:145-158.[Medline]
    59. 59
  59. Eisenstein, T. K., M. E. Hilburger, and D. M. P. Lawrence. 1996. Immunomodulation by morphine and other opioids, p. 103-120. In H. Friedman, T. W. Klein, and S. Specter (ed.), Drugs of abuse, immunity, and infections. CRC Press, Inc., Boca Raton, Fla.
    60. 60
  60. Eisenstein, T. K., J. J. Meissler, Jr., T. J. Rogers, E. B. Geller, and M. W. Adler. 1995. Mouse strain differences in immunosuppression by opioids in vitro. J. Pharmacol. Exp. Ther. 275:1484-1489.[Abstract/Free Full Text]
    61. 61
  61. Ewald, S. J., and H. Shao. 1993. Ethanol increases apoptotic cell death of thymocytes in vitro. Alcohol Clin. Exp. Res. 17:359-365.[CrossRef][Medline]
    62. 62
  62. Faubert, B. L., and N. E. Kaminski. 2000. AP-1 activity is negatively regulated by cannabinol through inhibition of its protein components, c-fos and c-jun. J. Leukoc. Biol. 67:259-266.[Abstract]
    63. 63
  63. Friedman, H. 1996. Drugs of abuse as possible co-factors in AIDS progression: summary of panel discussion. Adv. Exp. Med. Biol. 402:225-228.[Medline]
    64. 64
  64. Fuchs, B. A., and S. B. Pruett. 1993. Morphine induces apoptosis in murine thymocytes in vivo but not in vitro: involvement of both opiate and glucocorticoid receptors. J. Pharmacol. Exp. Ther. 266:417-423.[Abstract/Free Full Text]
    65. 65
  65. Gao, B. 2002. Interaction of alcohol and hepatitis viral proteins. implication in synergistic effect of alcohol drinking and viral hepatitis on liver injury. Alcohol 27:69-72.[CrossRef][Medline]
    66. 66
  66. Geng, Y., S. M. Savage, L. J. Johnson, J. Seagrave, and M. L. Sopori. 1995. Effects of nicotine on the immune response. I. Chronic exposure to nicotine impairs antigen receptor-mediated signal transduction in lymphocytes. Toxicol. Appl. Pharmacol. 135:268-278.[CrossRef][Medline]
    67. 67
  67. Geng, Y., S. M. Savage, S. Razani-Boroujerdi, and M. L. Sopori. 1996. Effects of nicotine on the immune response. II. Chronic nicotine treatment induces T cell anergy. J. Immunol. 156:2384-2390.[Abstract]
    68. 68
  68. Girouard, L., P. Mandrekar, D. Catalano, and G. Szabo. 1998. Regulation of monocyte interleukin-12 production by acute alcohol: a role for inhibition by interleukin-10. Alcohol Clin. Exp. Res. 22:211-216.[CrossRef][Medline]
    69. 69
  69. Goedert, J. J. 1984. Recreational drugs: relationship to AIDS. Ann. N. Y. Acad. Sci. 437:192-199.[CrossRef][Medline]
    70. 70
  70. Greenberg, S., J. Xie, J. Kolls, S. Nelson, P. Didier, and C. Mason. 1995. Ethanol suppresses Mycobacterium tuberculosis-induced mRNA for nitric oxide synthase in alveolar macrophages, in vivo. Alcohol Clin. Exp. Res. 19:394-401.[CrossRef][Medline]
    71. 71
  71. Grimm, M. C., A. Ben-Baruch, D. D. Taub, O. M. Howard, J. H. Resau, J. M. Wang, H. Ali, R. Richardson, R. Snyderman, and J. J. Oppenheim. 1998. Opiates transdeactivate chemokine receptors: delta and mu opiate receptor-mediated heterologous desensitization. J. Exp. Med. 188:317-325.[Abstract/Free Full Text]
    72. 72
  72. Guan, L., R. Townsend, T. K. Eisenstein, M. W. Adler, and T. J. Rogers. 1994. Both T cells and macrophages are targets of kappa-opioid-induced immunosuppression. Brain Behav. Immun. 8:229-240.[CrossRef][Medline]
    73. 73
  73. Gurwitz, D., and Y. Kloog. 1998. Do endogenous cannabinoids contribute to HIV-mediated immune failure? Mol. Med. Today 4:196-200.[CrossRef][Medline]
    74. 74
  74. Hakki, A., N. Hallquist, H. Friedman, and S. Pross. 2000. Differential impact of nicotine on cellular proliferation and cytokine production by LPS-stimulated murine splenocytes. Int. J. Immunopharmacol. 22:403-410.[CrossRef][Medline]
    75. 75
  75. Hallquist, N., A. Hakki, L. Wecker, H. Friedman, and S. Pross. 2000. Differential effects of nicotine and aging on splenocyte proliferation and the production of Th1- versus Th2-type cytokines. Proc. Soc. Exp. Biol. Med. 224:141-146.[Abstract/Free Full Text]
    76. 76
  76. Haverkos, H. W. 1988. Epidemiologic studies—Kaposi's sarcoma vs. opportunistic infections among homosexual men with AIDS. NIDA Res. Monogr. 83:96-105.[Medline]
    77. 77
  77. Haverkos, H. W., and J. W. Curran. 1982. The current outbreak of Kaposi's sarcoma and opportunistic infections. CA Cancer J. Clin. 32:330-339.[Free Full Text]
    78. 78
  78. Hernandez, M. C., L. R. Flores, and B. M. Bayer. 1993. Immunosuppression by morphine is mediated by central pathways. J. Pharmacol. Exp. Ther. 267:1336-1341.[Abstract/Free Full Text]
    79. 79
  79. Herring, A. C., and N. E. Kaminski. 1999. Cannabinol-mediated inhibition of nuclear factor-kappaB, cAMP response element-binding protein, and interleukin-2 secretion by activated thymocytes. J. Pharmacol. Exp. Ther. 291:1156-1163.[Abstract/Free Full Text]
    80. 80
  80. Hiemke, C., M. Stolp, S. Reuss, A. Wevers, S. Reinhardt, A. Maelicke, S. Schlegel, and H. Schroder. 1996. Expression of alpha subunit genes of nicotinic acetylcholine receptors in human lymphocytes. Neurosci. Lett. 214:171-174.[CrossRef][Medline]
    81. 81
  81. Hilburger, M. E., M. W. Adler, A. L. Truant, J. J. Meissler, Jr., V. Satishchandran, T. J. Rogers, and T. K. Eisenstein. 1997. Morphine induces sepsis in mice. J. Infect. Dis. 176:183-188.[Medline]
    82. 82
  82. Hoffman, K. E., K. A. Maslonek, L. A. Dykstra, and D. T. Lysle. 1995. Effects of central administration of morphine on immune status in Lewis and Wistar rats. Adv. Exp. Med. Biol. 373:155-159.[Medline]
    83. 83
  83. Houghtling, R. A., and B. M. Bayer. 2002. Rapid elevation of plasma interleukin-6 by morphine is dependent on autonomic stimulation of adrenal gland. J. Pharmacol. Exp. Ther. 300:213-219.[Abstract/Free Full Text]
    84. 84
  84. Houghtling, R. A., R. D. Mellon, R. J. Tan, and B. M. Bayer. 2000. Acute effects of morphine on blood lymphocyte proliferation and plasma IL-6 levels. Ann. N. Y. Acad. Sci. 917:771-777.[Medline]
    85. 85
  85. Howlett, A. C. 1995. Pharmacology of cannabinoid receptors. Annu. Rev. Pharmacol. Toxicol. 35:607-634.[CrossRef][Medline]
    86. 86
  86. Howlett, A. C., F. Barth, T. I. Bonner, G. Cabral, P. Casellas, W. A. Devane, C. C. Felder, M. Herkenham, K. Mackie, B. R. Martin, R. Mechoulam, and R. G. Pertwee. 2002. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol. Rev. 54:161-202.[Abstract/Free Full Text]
    87. 87
  87. Huber, G. L., V. E. Pochay, W. Pereira, J. W. Shea, W. C. Hinds, M. W. First, and G. C. Sornberger. 1980. Marijuana, tetrahydrocannabinol, and pulmonary antibacterial defenses. Chest 77:403-410.[Abstract/Free Full Text]
    88. 88
  88. Hudolin, V. 1975. Tuberculosis and alcoholism. Ann. N. Y. Acad. Sci. 252:353-364.[CrossRef][Medline]
    89. 89
  89. Hussey, H. H., and S. Katz. 1950. Infections resulting from narcotic addiction. Am. J. Med. 9:186.[CrossRef][Medline]
    90. 90
  90. Hussey, H. H., T. F. Keliber, B. B. Schaefer, and B. J. Walsh. 1944. Septicemia and bacterial endocarditis resulting from heroin addiction. JAMA 126:535.[Abstract/Free Full Text]
    91. 91
  91. Jaffe, J. H., and W. R. Martin. 1990. Opioid analgesics and antagonists. Permagon Press, Elmsford, N.Y.
    92. 92
  92. Jerrells, T. R. 2002. Association of alcohol consumption and exaggerated immunopathologic effects in the liver induced by infectious organism. Front. Biosci. 7:d1487-d1493.[Medline]
    93. 93
  93. Jerrells, T. R. 2002. Role of activated CD8(+) T cells in the initiation and continuation of hepatic damage. Alcohol 27:47-52.[CrossRef][Medline]
    94. 94
  94. Jerrells, T. R., A. J. Saad, and R. Domiati-Saad. 1992. Effects of ethanol on parameters of cellular immunity and host defense mechanisms to infectious agents. Alcohol 9:459-463.[CrossRef][Medline]
    95. 95
  95. Jerrells, T. R., and D. Sibley. 1995. Effects of ethanol on cellular immunity to facultative intracellular bacteria. Alcohol Clin. Exp. Res. 19:11-16.[CrossRef][Medline]
    96. 96
  96. Jerrells, T. R., D. A. Sibley, I. I. Slukvin, and K. A. Mitchell. 1998. Effects of ethanol consumption on mucosal and systemic T-cell-dependent immune responses to pathogenic microorganisms. Alcohol Clin. Exp. Res. 22:212S-215S.
    97. 97
  97. Jerrells, T. R., I. Slukvin, D. Sibley, and J. Fuseler. 1994. Increased susceptibility of experimental animals to infectious organisms as a consequence of ethanol consumption. Alcohol Suppl. 2:425-430.
    98. 98
  98. Jessop, J. J., and M. S. Taplits. 1991. Effect of high doses of morphine on Con-A induced lymphokine production in vitro. Immunopharmacology 22:175-184.[CrossRef][Medline]
    99. 99
  99. Joy, J. E., S. J. Watson, and J. A. Benson. 1999. Marijuana and medicine: assessing the science base. National Academy Press, Washington, D.C.
    100. 100
  100. Juel-Jensen, B. E. 1972. Cannabis and recurrent herpes simplex. Br. Med. J. 4:296.
    101. 101
  101. Kalra, R., S. P. Singh, S. M. Savage, G. L. Finch, and M. L. Sopori. 2000. Effects of cigarette smoke on immune response: chronic exposure to cigarette smoke impairs antigen-mediated signaling in T cells and depletes IP3-sensitive Ca(2+) stores. J. Pharmacol. Exp. Ther. 293:166-171.[Abstract/Free Full Text]
    102. 102
  102. Kaminski, N., W. S. Koh, K. H. Yang, M. Lee, and F. K. Kessler. 1994. Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G-protein coupled mechanism. Biochem. Pharm. 48:1899-1908.[CrossRef][Medline]
    103. 103
  103. Karch, S. R. (ed.). 1993. CRC Press, Inc., Boca Raton, Fla.
    104. 104
  104. Kawakami, Y., T. W. Klein, C. Newton, C. A. McCarthy, J. Djeu, G. Dennert, S. Specter, and H. Friedman. 1988. Suppression by cannabinoids of a cloned cell line with natural killer cell activity. Proc. Soc. Exp. Biol. Med. 187:355-359.[CrossRef][Medline]
    105. 105
  105. Kee, T. H. 1908. The habitual use of opium as a factor in the production of diseases. Philipp. J. Sci. 6:63.
    106. 106
  106. Klein, T., H. Friedman, and S. Specter. 1998. Marijuana, immunity and infection. J. Neuroimmunol. 83:102-115.[CrossRef][Medline]
    107. 107
  107. Klein, T. W., and H. Friedman. 1990. Modulation of murine immune cell function by marijuana components, p. 87-111. In R. Watson (ed.), Drugs of abuse and immune function. CRC Press, Inc., Boca Raton, Fla.
    108. 108
  108. Klein, T. W., B. Lane, C. A. Newton, and H. Friedman. 2000. The cannabinoid system and cytokine network. Proc. Soc. Exp. Biol. Med. 225:1-8.[Abstract/Free Full Text]
    109. 109
  109. Klein, T. W., K. Matsui, C. A. Newton, J. Young, R. E. Widen, and H. Friedman. 1993. Cocaine suppresses proliferation of phytohemagglutinin-activated human peripheral blood T-cells. Int. J. Immunopharmacol. 15:77-86.[CrossRef][Medline]
    110. 110
  110. Klein, T. W., C. Newton, and H. Friedman. 1987. Inhibition of natural killer cell function by marijuana components. J. Toxicol. Environ. Health 20:321-332.[Medline]
    111. 111
  111. Klein, T. W., C. Newton, R. Widen, and H. Friedman. 1993. {Delta}9-Tetrahydrocannabinol injection induces cytokine-mediated mortality of mice infected with Legionella pneumophila. J. Pharmacol. Exp. Ther. 267:635-640.[Abstract/Free Full Text]
    112. 112
  112. Klein, T. W., C. A. Newton, N. Nakachi, and H. Friedman. 2000. {Delta}9-tetrahydrocannabinol treatment suppresses immunity and early IFN-{gamma}, IL-12, and IL-12 receptor ß2 responses to Legionella pneumophila infection. J. Immunol. 164:6461-6466.[Abstract/Free Full Text]
    113. 113
  113. Klein, T. W., C. A. Newton, R. Widen, and H. Friedman. 1985. The effect of delta-9-tetrahydrocannabinol and 11-hydroxy-delta-9-tetrahydrocannabinol on T lymphocyte and B lymphocyte mitogen responses. J. Immunopharmacol. 7:451-466.[Medline]
    114. 114
  114. Kolls, J. K., J. Xie, D. Lei, S. Greenberg, W. R. Summer, and S. Nelson. 1995. Differential effects of in vivo ethanol on LPS-induced TNF and nitric oxide production in the lung. Am. J. Physiol. 268:L991-L998.
    115. 115
  115. Kraft, A., and N. M. Leitch. 1921. The action of drugs in infection, the influence of morphine in experimental septicemia. J. Pharmacol. Exp. Ther. 17:377.[Free Full Text]
    116. 116
  116. Kruegar, H., N. B. Eddy, and M. Sumwalt. 1941. The pharmacology of opium alkaloids. Public Health Rep. 165(Suppl.):415.
    117. 117
  117. Lange, W. R., J. C. Ball, M. B. Pfeiffer, F. R. Snyder, and E. J. Cone. 1989. The Lexington addicts, 1971-1972: demographic characteristics, drug use patterns, and selected infectious disease experience. Int. J. Addict. 24:609-626.[Medline]
    118. 118
  118. Lebargy, F., K. Benhammou, D. Morin, R. Zini, S. Urien, F. Bree, J. Bignon, A. Branellec, and G. Lagrue. 1996. Tobacco smoking induces expression of very-high-affinity nicotine binding sites on blood polymorphonuclear cells. Am. J. Respir. Crit. Care Med. 153:1056-1063.[Abstract]
    119. 119
  119. Lee, S. F., C. Newton, R. Widen, H. Friedman, and T. W. Klein. 2001. Differential expression of cannabinoid CB2 receptor mRNA in mouse immune cell subpopulations and following B cell stimulation. Eur. J. Pharmacol. 423:235-241.[CrossRef][Medline]
    120. 120
  120. Lefkowitz, S. S., and C. Y. Chiang. 1975. Effects of certain abused drugs on hemolysin forming cells. Life Sci. 17:1763-1767.[CrossRef][Medline]
    121. 121
  121. Liu, Y., D. J. Blackbourn, L. F. Chuang, K. F. Killam, Jr., and R. Y. Chuang. 1992. Effects of in vivo and in vitro administration of morphine sulfate upon rhesus macaque polymorphonuclear cell phagocytosis and chemotaxis. J. Pharmacol. Exp. Ther. 263:533-539.[Abstract/Free Full Text]
    122. 122
  122. Liu, Y., B. B. Whitlock, J. A. Pultz, and S. A. Wolfe, Jr. 1995. Sigma-1 receptors modulate functional activity of rat splenocytes. J. Neuroimmunol. 59:143-154.[CrossRef][Medline]
    123. 123
  123. Louria, D. B., T. Hensle, and J. Rose. 1967. The major medical complications of heroin addiction. Ann. Intern. Med. 67:1-22.
    124. 124
  124. Lyman, W. D. 1993. Perinatal AIDS: drugs of abuse and transplacental infection. Adv. Exp. Med. Biol. 335:211-217.[Medline]
    125. 125
  125. Lysle, D. T., M. E. Coussons, V. J. Watts, E. H. Bennett, and L. A. Dykstra. 1993. Morphine-induced alterations of immune status: dose dependency, compartment specificity and antagonism by naltrexone. J. Pharmacol. Exp. Ther. 265:1071-1078.[Abstract/Free Full Text]
    126. 126
  126. Lysle, D. T., K. E. Hoffman, and L. A. Dykstra. 1996. Evidence for the involvement of the caudal region of the periaqueductal gray in a subset of morphine-induced alterations of immune status. J. Pharmacol. Exp. Ther. 277:1533-1540.[Abstract/Free Full Text]
    127. 127
  127. MacFarlane, A. S., X. Peng, J. J. Meissler, Jr., T. J. Rogers, E. B. Geller, M. W. Adler, and T. K. Eisenstein. 2000. Morphine increases susceptibility to oral Salmonella typhimurium infection. J. Infect. Dis. 181:1350-1358.[CrossRef][Medline]
    128. 128
  128. MacGregor, R. R., and D. B. Louria. 1997. Alcohol and infection. Curr. Clin. Top. Infect. Dis. 17:291-315.[Medline]
    129. 129
  129. Mandrekar, P., D. Catalano, and G. Szabo. 1999. Inhibition of lipopolysaccharide-mediated NFkappaB activation by ethanol in human monocytes. Int. Immunol. 11:1781-1790.[Abstract/Free Full Text]
    130. 130
  130. Mansell, P. W. 1984. Acquired immune deficiency syndrome, leading to opportunistic infections, Kaposi's sarcoma, and other malignancies. Crit. Rev. Clin. Lab. Sci. 20:191-204.[Medline]
    131. 131
  131. Mao, J. T., M. Huang, J. Wang, S. Sharma, D. P. Tashkin, and S. M. Dubinett. 1996. Cocaine down-regulates IL-2-induced peripheral blood lymphocyte IL-8 and IFN-{gamma} production. Cell. Immunol. 172:217-223.[CrossRef][Medline]
    132. 132
  132. Mao, J. T., L. X. Zhu, S. Sharma, K. Chen, M. Huang, S. J. Santiago, J. Gulsurd, D. P. Tashkin, and S. M. Dubinett. 1997. Cocaine inhibits human endothelial cell IL-8 production: the role of transforming growth factor-beta. Cell. Immunol. 181:38-43.[CrossRef][Medline]
    133. 133
  133. Massi, P., D. Fuzio, D. Vigano, P. Sacerdote, and D. Parolaro. 2000. Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer activity. Eur. J. Pharmacol. 387:343-347.[CrossRef][Medline]
    134. 134
  134. Matsuda, L. A., S. J. Lolait, M. J. Brownstein, A. C. Young, and T. I. Bonner. 1990. Structure of cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561-564.[CrossRef][Medline]
    135. 135
  135. Matsumoto, R. R., K. A. McCracken, B. Pouw, Y. Zhang, and W. D. Bowen. 2002. Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides. Neuropharmacology 42:1043-1055.[CrossRef][Medline]
    136. 136
  136. Matsunaga, K., T. W. Klein, H. Friedman, and Y. Yamamoto. 2001. Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine. J. Immunol. 167:6518-6524.[Abstract/Free Full Text]
    137. 137
  137. Maurice, T., R. Martin-Fardon, P. Romieu, and R. R. Matsumoto. 2002. Sigma(1) (sigma(1)) receptor antagonists represent a new strategy against cocaine addiction and toxicity. Neurosci. Biobehav. Rev. 26:499-527.[CrossRef][Medline]
    138. 138
  138. McAllister, S. D., and M. Glass. 2002. CB(1) and CB(2) receptor-mediated signalling: a focus on endocannabinoids. Prostaglandins Leukotrienes Essent. Fatty Acids 66:161-171.[CrossRef][Medline]
    139. 139
  139. McCarthy, L., M. Wetzel, J. K. Sliker, T. K. Eisenstein, and T. J. Rogers. 2001. Opioids, opioid receptors, and the immune response. Drug Alcohol Depend. 62:111-123.[CrossRef][Medline]
    140. 140
  140. McKallip, R. J., C. Lombard, B. R. Martin, M. Nagarkatti, and P. S. Nagarkatti. 2002. Delta(9)-tetrahydrocannabinol-induced apoptosis in the thymus and spleen as a mechanism of immunosuppression in vitro and in vivo. J. Pharmacol. Exp. Ther. 302:451-465.[Abstract/Free Full Text]
    141. 141
  141. Meadows, G. G., S. E. Blank, and D. D. Duncan. 1989. Influence of ethanol consumption on natural killer cell activity in mice. Alcohol Clin. Exp. Res. 13:476-479.[CrossRef][Medline]
    142. 142
  142. Mechoulam, R., S. Ben-Shabat, L. Hanus, M. Ligumsky, N. E. Kaminski, A. R. Schatz, A. Gopher, S. Almog, B. R. Martin, D. R. Compton, R. G. Pertwee, G. Griffin, M. Bayewitch, J. Barg, and Z. Vogel. 1995. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharm. 50:83-90.[CrossRef][Medline]
    143. 143
  143. Mechoulam, R., Z. Ben-Zvi, B. Yagnitinsky, and A. Shani. 1969. A new tetrahydrocannabinolic acid. Tetrahedron. Lett. 28:2339-2341.[Medline]
    144. 144
  144. Mellon, R. D., and B. M. Bayer. 1998. Evidence for central opioid receptors in the immunomodulatory effects of morphine: review of potential mechanism(s) of action. J. Neuroimmunol. 83:19-28.[CrossRef][Medline]
    145. 145
  145. Mendenhall, C. L., C. J. Grossman, G. A. Roselle, S. Ghosn, P. S. Gartside, S. D. Rouster, P. V. Chalasani, G. Schmitt, K. Martin, and K. Lamping. 1990. Host response to mycobacterial infection in the alcoholic rat. Gastroenterology 99:1723-1726.[Medline]
    146. 146
  146. Meyerhoff, D. J. 2001. Effects of alcohol and HIV infection on the central nervous system. Alcohol Res. Health 25:288-298.[Medline]
    147. 147
  147. Mishkin, E. M., and G. A. Cabral. 1985. Delta-9-tetrahydrocannabinol decreases host resistance to herpes simplex virus type 2 vaginal infection in the B6C3F1 mouse. J. Gen. Virol. 66:2539-2549.[Abstract/Free Full Text]
    148. 148
  148. Molitor, T. W., A. Morilla, J. M. Risdahl, M. P. Murtaugh, C. C. Chao, and P. K. Peterson. 1992. Chronic morphine administration impairs cell-mediated immune responses in swine. J. Pharmacol. Exp. Ther. 260:581-586.[Abstract/Free Full Text]
    149. 149
  149. Morahan, P. S., P. C. Klykken, S. H. Smith, L. S. Harris, and A. E. Munson. 1979. Effects of cannabinoids on host resistance to Listeria monocytogenes and herpes simplex virus. Infect. Immun. 23:670-674.[Abstract/Free Full Text]
    150. 150
  150. Moskowitz, L. B., P. Kory, J. C. Chan, H. W. Haverkos, F. K. Conley, and G. T. Hensley. 1983. Unusual causes of death in Haitians residing in Miami. High prevalence of opportunistic infections. JAMA 250:1187-1191.[Abstract/Free Full Text]
    151. 151
  151. Munro, S., K. L. Thomas, and M. Abu-Shaar. 1993. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61-65.[CrossRef][Medline]
    152. 152
  152. Mutchnick, M. G., and H. H. Lee. 1988. Impaired lymphocyte proliferative response to mitogen in alcoholic patients. Absence of a relation to liver disease activity. Alcohol Clin. Exp. Res. 12:155-158.[CrossRef][Medline]
    153. 153
  153. Nahas, G. G., A. Morishima, and B. Desoize. 1977. Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes. Fed. Proc. 36:1748-1752.[Medline]
    154. 154
  154. Nahas, G. G., N. Suciu-Foca, J.-P. Armand, and A. Morishima. 1974. Inhibition of cellular mediated immunity in marihuana smokers. Science 183:419-420.[Abstract/Free Full Text]
    155. 155
  155. Nahas, G. G., D. Zagury, and I. W. Schwartz. 1973. Evidence for the possible immunogenicity of {Delta}9-tetrahydrocannabinol (THC) in rodents. Nature 243:407-408.[CrossRef][Medline]
    156. 156
  156. Nair, M. P., Z. A. Kronfol, and S. A. Schwartz. 1990. Effects of alcohol and nicotine on cytotoxic functions of human lymphocytes. Clin. Immunol. Immunopathol. 54:395-409.[CrossRef][Medline]
    157. 157
  157. Nalpas, B., S. Pol, V. Thepot, H. Zylberberg, P. Berthelot, and C. Brechot. 1998. ESBRA 1997 Award lecture: relationship between excessive alcohol drinking and viral infections. Alcohol 33:202-206.
    158. 158
  158. Nelson, S., G. Bagby, and W. R. Summer. 1989. Alcohol suppresses lipopolysaccharide-induced tumor necrosis factor activity in serum and lung. Life Sci. 44:673-676.[CrossRef][Medline]
    159. 159
  159. Nelson, S., and J. K. Kolls. 2002. Alcohol, host defense and society. Nat. Rev. Immunol. 2:205-209.[CrossRef][Medline]
    160. 160
  160. Nelson, S., C. Mason, G. Bagby, and W. Summer. 1995. Alcohol, tumor necrosis factor, and tuberculosis. Alcohol Clin. Exp. Res. 19:17-24.[CrossRef][Medline]
    161. 161
  161. Newell, G. R., P. W. Mansell, M. R. Spitz, J. M. Reuben, and E. M. Hersh. 1985. Volatile nitrites. Use and adverse effects related to the current epidemic of the acquired immune deficiency syndrome. Am. J. Med. 78:811-816.[CrossRef][Medline]
    162. 162
  162. Newton, C., T. Klein, and H. Friedman. 1998. The role of macrophages in THC-induced alteration of the cytokine network. Adv. Exp. Med. Biol. 437:207-214.[Medline]
    163. 163
  163. Newton, C. A., T. W. Klein, and H. Friedman. 1994. Secondary immunity to Legionella pneumophila and Th1 activity are suppressed by delta-9-tetrahydrocannabinol injection. Infect. Immun. 62:4015-4020.[Abstract/Free Full Text]
    164. 164
  164. Nieman, R. B., J. Fleming, R. J. Coker, J. R. Harris, and D. M. Mitchell. 1993. The effect of cigarette smoking on the development of AIDS in HIV-1-seropositive individuals. Aids 7:705-710.[Medline]
    165. 165
  165. Osler, W. 1880. Oedema of the left lung in morphia poisoning. Montreal Gen. Hosp. Rep. 1:291.
    166. 166
  166. Ou, D. W., M. L. Shen, and Y. D. Luo. 1989. Effects of cocaine on the immune system of Balb/C mice. Clin. Immunol. Immunopathol. 52:305-312.[CrossRef][Medline]
    167. 167
  167. Ouyang, Y., N. Virasch, P. Hao, M. T. Aubrey, N. Mukerjee, B. E. Bierer, and B. M. Freed. 2000. Suppression of human IL-1ß, IL-2, IFN-{gamma}, and TNF-{alpha} production by cigarette smoke extracts. J Allergy Clin. Immunol. 106:280-287.
    168. 168
  168. Pacifici, R., S. Di Carlo, A. Bacosi, and P. Zuccaro. 1993. Macrophage functions in drugs of abuse-treated mice. Int. J. Immunopharmacol. 15:711-716.[CrossRef][Medline]
    169. 169
  169. Panaslak, W., S. Gumulka, M. Kobus, and M. Luczak. 1990. The influence of morphine on development of HSV-1 and M-MSV virus infection in mice. Acta Microbiol. Pol. 39:215-218.[Medline]
    170. 170
  170. Paradise, L. J., and H. Friedman. 1993. Syphilis and drugs of abuse. Adv. Exp. Med. Biol. 335:81-87.[Medline]
    171. 171
  171. Pellegrino, T. C., K. L. Dunn, and B. M. Bayer. 2001. Mechanisms of cocaine-induced decreases in immune cell function. Int. Immunopharmacol. 1:665-675.[CrossRef][Medline]
    172. 172
  172. Peng, X., J. J. Cebra, M. W. Adler, J. J. Meissler, Jr., A. Cowan, P. Feng, and T. K. Eisenstein. 2001. Morphine inhibits mucosal antibody responses and TGF-beta mRNA in gut-associated lymphoid tissue following oral cholera toxin in mice. J. Immunol. 167:3677-3681.[Abstract/Free Full Text]
    173. 173
  173. Peng, X., D. M. Mosser, M. W. Adler, T. J. Rogers, J. J. Meissler, Jr., and T. K. Eisenstein. 2000. Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages. J. Leukoc. Biol. 68:723-728.[Abstract/Free Full Text]
    174. 174
  174. Pertwee, R. G. 1997. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Ther. 74:129-180.[CrossRef][Medline]
    175. 175
  175. Peterson, J. D., K. Vasquez, and C. Waltenbaugh. 1998. Interleukin-12 therapy restores cell-mediated immunity in ethanol-consuming mice. Alcohol Clin. Exp. Res. 22:245-251.[CrossRef][Medline]
    176. 176
  176. Peterson, P. K., G. Gekker, C. Brummitt, P. Pentel, M. Bullock, M. Simpson, J. Hitt, and B. Sharp. 1989. Suppression of human peripheral blood mononuclear cell function by methadone and morphine. J. Infect. Dis. 159:480-487.[Medline]
    177. 177
  177. Peterson, P. K., G. Gekker, C. C. Chao, R. Schut, T. W. Molitor, and H. H. Balfour, Jr. 1991. Cocaine potentiates HIV-1 replication in human peripheral blood mononuclear cell cocultures. Involvement of transforming growth factor-beta. J. Immunol. 146:81-84.[Abstract]
    178. 178
  178. Peterson, P. K., G. Gekker, S. Hu, W. S. Sheng, T. W. Molitor, and C. C. Chao. 1995. Morphine stimulates phagocytosis of Mycobacterium tuberculosis by human microglial cells: involvement of a G protein-coupled opiate receptor. Adv. Neuroimmunol. 5:299-309.[CrossRef][Medline]
    179. 179
  179. Peterson, P. K., B. Sharp, G. Gekker, C. Brummitt, and W. F. Keane. 1987. Opioid-mediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells. J. Clin. Investig. 80:824-831.
    180. 180
  180. Pontieri, F. E., G. Tanda, F. Orzi, and G. Di Chiara. 1996. Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382:255-257.[CrossRef][Medline]
    181. 181
  181. Pross, S. H., T. W. Klein, C. A. Newton, J. Smith, R. Widen, and H. Friedman. 1990. Differential suppression of T-cell subpopulations by THC (delta-9-tetrahydrocannabinol). Int. J. Immunopharmacol. 12:539-544.[CrossRef][Medline]
    182. 182
  182. Pross, S. H., Y. Nakano, R. Widen, S. McHugh, C. A. Newton, T. W. Klein, and H. Friedman. 1992. Differing effects of delta-9-tetrahydrocannabinol (THC) on murine spleen cell populations dependent upon stimulators. Int. J. Immunopharmacol. 14:1019-1027.[CrossRef][Medline]
    183. 183
  183. Pruett, S. B., Y. C. Han, and B. A. Fuchs. 1992. Morphine suppresses primary humoral immune responses by a predominantly indirect mechanism. J. Pharmacol. Exp. Ther. 262:923-928.[Abstract/Free Full Text]
    184. 184
  184. Rahim, R. T., J. J. Meissler, Jr., A. Cowan, T. J. Rogers, E. B. Geller, J. Gaughan, M. W. Adler, and T. K. Eisenstein. 2001. Administration of mu-, kappa- or delta2-receptor agonists via osmotic mini pumps suppresses murine splenic antibody responses. Int. Immunopharmacol. 1:2001-2009.[CrossRef][Medline]
    185. 185
  185. Reichman, L. B., C. P. Felton, and J. R. Edsall. 1979. Drug dependence, a possible new risk factor for tuberculosis disease. Arch. Intern. Med. 139:337-339.[Abstract/Free Full Text]
    186. 186
  186. Reisine, T., and G. I. Bell. 1993. Molecular biology of opioid receptors. Trends Neurosci. 16:506-510.[CrossRef][Medline]
    187. 187
  187. Reynolds, L., and B. C. Cantab. 1910. The influence of narcotics on phagocytosis. Lancet 178:569.[CrossRef]
    188. 188
  188. Risdahl, J. M., K. V. Khanna, P. K. Peterson, and T. W. Molitor. 1998. Opiates and infection. J. Neuroimmunol. 83:4-18.[CrossRef][Medline]
    189. 189
  189. Risdahl, J. M., P. K. Peterson, C. C. Chao, C. Pijoan, and T. W. Molitor. 1993. Effects of morphine dependence on the pathogenesis of swine herpesvirus infection. J. Infect. Dis. 167:1281-1287.[Medline]
    190. 190
  190. Risdahl, J. M., P. K. Peterson, and T. W. Molitor. 1996. Opiates, infection and immunity, p. 1-42. In H. Friedman, T. W. Klein, and S. Specter (ed.), Drugs of abuse, immunity, and infections. CRC Press, Inc., Boca Raton, Fla.
    191. 191
  191. Rojavin, M., I. Szabo, J. L. Bussiere, T. J. Rogers, M. W. Adler, and T. K. Eisenstein. 1993. Morphine treatment in vitro or in vivo decreases phagocytic functions of murine macrophages. Life Sci. 53:997-1006.[CrossRef][Medline]
    192. 192
  192. Roth, M. D., D. P. Tashkin, R. Choi, B. D. Jamieson, J. A. Zack, and G. C. Baldwin. 2002. Cocaine enhances human immunodeficiency virus replication in a model of severe combined immunodeficient mice implanted with human peripheral blood leukocytes. J. Infect. Dis. 185:701-705.[CrossRef][Medline]
    193. 193
  193. Roy, S., S. Balasubramanian, S. Sumandeep, R. Charboneau, J. Wang, D. Melnyk, G. J. Beilman, R. Vatassery, and R. A. Barke. 2001. Morphine directs T cells toward T(H2) differentiation. Surgery 130:304-309.[CrossRef][Medline]
    194. 194
  194. Roy, S., R. A. Barke, and H. H. Loh. 1998. Mu-opioid receptor-knockout mice: role of mu-opioid receptor in morphine mediated immune functions. Brain Res. Mol. Brain Res. 61:190-194.[Medline]
    195. 195
  195. Roy, S., R. G. Charboneau, and R. A. Barke. 1999. Morphine synergizes with lipopolysaccharide in a chronic endotoxemia model. J. Neuroimmunol. 95:107-114.[CrossRef][Medline]
    196. 196
  196. Ruiz, M., S. Ewig, M. A. Marcos, J. A. Martinez, F. Arancibia, J. Mensa, and A. Torres. 1999. Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity. Am. J. Respir. Crit. Care Med. 160:397-405.[Abstract/Free Full Text]
    197. 197
  197. Saad, A. J., R. Domiati-Saad, and T. R. Jerrells. 1993. Ethanol ingestion increases susceptibility of mice to Listeria monocytogenes. Alcohol Clin. Exp. Res. 17:75-85.[CrossRef][Medline]
    198. 198
  198. Schatz, A. R., W. S. Koh, and N. E. Kaminski. 1993. {Delta}9-Tetrahydrocannabinol selectively inhibits T-cell dependent humoral immune responses through direct inhibition of accessory T-cell function. Immunopharmacology 26:129-137.[CrossRef][Medline]
    199. 199
  199. Scott, J. M. 1969. The white poppy. A history of opium. Cox and Wyman Ltd., London, England.
    200. 200
  200. Sei, Y., T. McIntyre, E. Fride, K. Yoshimoto, P. Skolnick, and P. K. Arora. 1991. Inhibition of calcium mobilization is an early event in opiate-induced immunosuppression. FASEB J. 5:2194-2199.[Abstract]
    201. 201
  201. Sei, Y., K. Yoshimoto, T. McIntyre, P. Skolnick, and P. K. Arora. 1991. Morphine-induced thymic hypoplasia is glucocorticoid-dependent. J. Immunol. 146:194-198.[Abstract]
    202. 202
  202. Sepulveda, R. T., S. Jiang, D. G. Besselsen, and R. R. Watson. 2002. Alcohol consumption during murine acquired immunodeficiency syndrome accentuates heart pathology due to Coxsackievirus. Alcohol 37:157-163.
    203. 203
  203. Shahabi, N. A., and B. M. Sharp. 1995. Antiproliferative effects of delta opioids on highly purified CD4+ and CD8+ murine T cells. J. Pharmacol. Exp. Ther. 273:1105-1113.[Abstract/Free Full Text]
    204. 204
  204. Shahbazian, L. M., H. R. Darban, J. R. Darban, A. M. Stazzone, and R. R. Watson. 1992. Influence of the level of dietary ethanol in mice with murine AIDS on resistance to Streptococcus pneumoniae. Alcohol 27:345-352.
    205. 205
  205. Sharkey, J., K. A. Glen, S. Wolfe, and M. J. Kuhar. 1988. Cocaine binding at sigma receptors. Eur. J. Pharmacol. 149:171-174.[CrossRef][Medline]
    206. 206
  206. Shavit, Y., A. Depaulis, F. C. Martin, G. W. Terman, R. N. Pechnick, C. J. Zane, R. P. Gale, and J. C. Liebeskind. 1986. Involvement of brain opiate receptors in the immune-suppressive effect of morphine. Proc. Natl. Acad. Sci. USA 83:7114-7117.[Abstract/Free Full Text]
    207. 207
  207. Shavit, Y., F. C. Martin, R. Yirmiya, S. Ben-Eliyahu, G. W. Terman, H. Weiner, R. P. Gale, and J. C. Liebeskind. 1987. Effects of a single administration of morphine or foot shock stress on natural killer cell cytotoxicity. Brain Behav. Immun. 1:318-328.[CrossRef][Medline]
    208. 208
  208. Sibley, D., and T. R. Jerrells. 2000. Alcohol consumption by C57BL/6 mice is associated with depletion of lymphoid cells from the gut-associated lymphoid tissues and altered resistance to oral infections with Salmonella typhimurium. J. Infect. Dis. 182:482-489.[CrossRef][Medline]
    209. 209
  209. Sibley, D. A., J. Fuseler, I. Slukvin, and T. R. Jerrells. 1995. Ethanol-induced depletion of lymphocytes from the mesenteric lymph nodes of C57BL/6 mice is associated with RNA but not DNA degradation. Alcohol Clin. Exp. Res. 19:324-331.[CrossRef][Medline]
    210. 210
  210. Sibley, D. A., N. Osna, C. Kusynski, L. Wilkie, and T. R. Jerrells. 2001. Alcohol consumption is associated with alterations in macrophage responses to interferon-{gamma} and infection by Salmonella typhimurium. FEMS Immunol. Med. Microbiol. 32:73-83.[Medline]
    211. 211
  211. Sidney, S., J. E. Beck, I. S. Tekawa, C. P. Quesenberry, and G. D. Friedmen. 1997. Marijuana use and mortality. Am. J. Public Health 87:585-590.[Abstract/Free Full Text]
    212. 212
  212. Siegel, L. 1986. AIDS: relationship to alcohol and other drugs. J. Subst. Abuse Treat. 3:271-274.[CrossRef][Medline]
    213. 213
  213. Slavinsky, J., III, T. Myers, R. K. Swoboda, J. E. Leigh, S. Hager, and P. L. Fidel, Jr. 2002. Th1/Th2 cytokine profiles in saliva of HIV-positive smokers with oropharyngeal candidiasis. Oral Microbiol. Immunol. 17:38-43.[CrossRef][Medline]
    214. 214
  214. Smith, M. S., Y. Yamamoto, C. A. Newton, H. Friedman, and T. W. Klein. 1997. Psychoactive cannabinoids increase mortality and alter acute phase cytokine responses in mice sublethally infected with Legionella pneumophila. Proc. Soc. Exp. Biol. Med. 214:69-75.[CrossRef][Medline]
    215. 215
  215. Smith, S. R., C. Terminelli, and G. Denhardt. 2000. Effects of cannabinoid receptor agonist and antagonist ligands on production of inflammatory cytokines and anti-inflammatory interleukin-10 in endotoxemic mice. J. Pharmacol. Exp. Ther. 293:136-150.[Abstract/Free Full Text]
    216. 216
  216. Sopori, M. 2002. Effects of cigarette smoke on the immune system. Nat. Rev. Immunol. 2:372-377.[CrossRef][Medline]
    217. 217
  217. Sopori, M. L., and W. Kozak. 1998. Immunomodulatory effects of cigarette smoke. J. Neuroimmunol. 83:148-156.[CrossRef][Medline]
    218. 218
  218. Sopori, M. L., W. Kozak, S. M. Savage, Y. Geng, D. Soszynski, M. J. Kluger, E. K. Perryman, and G. E. Snow. 1998. Effect of nicotine on the immune system: possible regulation of immune responses by central and peripheral mechanisms. Psychoneuroendocrinology 23:189-204.[CrossRef][Medline]
    219. 219
  219. Specter, S., T. W. Klein, C. Newton, M. Mondragon, R. Widen, and H. Friedman. 1986. Marijuana effects on immunity: suppression of human natural killer cell activity by delta-9-tetrahydrocannabinol. Int. J. Immunopharmacol. 8:741-745.[CrossRef][Medline]
    220. 220
  220. Specter, S., and G. Lancz. 1991. Effects of marijuana on human natural killer cell activity. Adv. Exp. Med. Biol. 288:47-56.[Medline]
    221. 221
  221. Specter, S., G. Lancz, and J. Hazelden. 1990. Marijuana and immunity: tetrahydrocannabinol mediated inhibition of lymphocyte blastogenesis. Int. J. Immunopharmacol. 12:261-267.[CrossRef][Medline]
    222. 222
  222. Specter, S., G. Lancz, G. Westrich, and H. Friedman. 1991. Delta-9-tetrahydrocannabinol augments murine retroviral inducted immunosuppression and infection. Int. J. Immunopharmacol. 13:411-417.[CrossRef][Medline]
    223. 223
  223. Srivastava, M. D., B. I. S. Srivastava, and B. Brouhard. 1998. {Delta}9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology 40:179-185.[CrossRef][Medline]
    224. 224
  224. Starec, M., B. Rouveix, M. Sinet, F. Chau, B. Desforges, J. J. Pocidalo, and P. Lechat. 1991. Immune status and survival of opiate- and cocaine-treated mice infected with Friend virus. J. Pharmacol. Exp. Ther. 259:745-750.[Abstract/Free Full Text]
    225. 225
  225. Sternbach, G. L. 1990. Infections in alcoholic patients. Emerg. Med. Clin. North Am. 8:793-803.[Medline]
    226. 226
  226. Stoltz, D. A., S. Nelson, J. K. Kolls, P. Zhang, R. P. Bohm, Jr., M. Murphy-Corb, and G. J. Bagby. 2000. In vitro ethanol suppresses alveolar macrophage TNF-{alpha} during simian immunodeficiency virus infection. Am. J. Respir. Crit. Care Med. 161:135-140.[Abstract/Free Full Text]
    227. 227
  227. Stoneburner, R. L., D. C. Des Jarlais, D. Benezra, L. Gorelkin, J. L. Sotheran, S. R. Friedman, S. Schultz, M. Marmor, D. Mildvan, and R. Maslansky. 1998. A larger spectrum of severe HIV-1-related disease in intravenous drug users in New York City. Science 242:916-919.
    228. 228
  228. Su, T. P. 1991. Sigma receptors. Putative links between nervous, endocrine and immune systems. Eur. J. Biochem. 200:633-642.[Medline]
    229. 229
  229. Swanson, M. A., W. T. Lee, and V. M. Sanders. 2001. IFN-{gamma} production by Th1 cells generated from naive CD4+ T cells exposed to norepinephrine. J. Immunol. 166:232-240.[Abstract/Free Full Text]
    230. 230
  230. Szabo, G. 1999. Consequences of alcohol consumption on host defence. Alcohol 34:830-841.
    231. 231
  231. Szabo, G., L. Girouard, P. Mandrekar, and D. Catalano. 1998. Regulation of monocyte IL-12 production: augmentation by lymphocyte contact and acute ethanol treatment, inhibition by elevated intracellular cAMP. Int. J. Immunopharmacol. 20:491-503.[CrossRef][Medline]
    232. 232
  232. Szabo, G., P. Mandrekar, A. Dolganiuc, D. Catalano, and K. Kodys. 2001. Reduced alloreactive T-cell activation after alcohol intake is due to impaired monocyte accessory cell function and correlates with elevated IL-10, IL-13, and decreased IFN{gamma} levels. Alcohol Clin. Exp. Res. 25:1766-1772.[CrossRef][Medline]
    233. 233
  233. Szabo, G., B. Verma, and D. Catalano. 1993. Selective inhibition of antigen-specific T lymphocyte proliferation by acute ethanol exposure: the role of impaired monocyte antigen presentation capacity and mediator production. J. Leukoc. Biol. 54:534-544.[Abstract]
    234. 234
  234. Szabo, G., B. K. Verma, M. Fogarasi, and D. E. Catalano. 1992. Induction of transforming growth factor-beta and prostaglandin E2 production by ethanol in human monocytes. J. Leukoc. Biol. 52:602-610.[Abstract]
    235. 235
  235. Szabo, I., M. Rojavin, J. L. Bussiere, T. K. Eisenstein, M. W. Adler, and T. J. Rogers. 1993. Suppression of peritoneal macrophage phagocytosis of Candida albicans by opioids. J. Pharmacol. Exp. Ther. 267:703-706.[Abstract/Free Full Text]
    236. 236
  236. Tanda, G., F. E. Pontieri, and G. Di Chiara. 1997. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science 276:2048-2050.[Abstract/Free Full Text]
    237. 237
  237. Taub, D. D., T. K. Eisenstein, E. B. Geller, M. W. Adler, and T. J. Rogers. 1991. Immunomodulatory activity of mu- and kappa-selective opioid agonists. Proc. Natl. Acad. Sci. USA 88:360-364.[Abstract/Free Full Text]
    238. 238
  238. Thomas, P. T., R. V. House, and H. N. Bhargava. 1995. Direct cellular immunomodulation produced by diacetylmorphine (heroin) or methadone. Gen. Pharmacol. 26:123-130.[Medline]
    239. 239
  239. Tubaro, E., U. Avico, C. Santiangeli, P. Zuccaro, G. Cavallo, R. Pacifici, C. Croce, and G. Borelli. 1985. Morphine and methadone impact on human phagocytic physiology. Int. J. Immunopharmacol. 7:865-874.[CrossRef][Medline]
    240. 240
  240. Tubaro, E., G. Borelli, C. Croce, G. Cavallo, and C. Santiangeli. 1983. Effect of morphine on resistance to infection. J. Infect. Dis. 148:656-666.[Medline]
    241. 241
  241. Valjent, E., C. Pages, M. Rogard, M. J. Besson, R. Maldonado, and J. Caboche. 2001. Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission. Eur. J. Neurosci. 14:342-352.[CrossRef][Medline]
    242. 242
  242. Veyries, M. L., M. Sinet, B. Desforges, and B. Rouveix. 1995. Effects of morphine on the pathogenesis of murine Friend retrovirus infection. J. Pharmacol. Exp. Ther. 272:498-504.[Abstract/Free Full Text]
    243. 243
  243. Vlahov, D., J. C. Anthony, D. Celentano, L. Solomon, and N. Chowdhury. 1991. Trends of HIV-1 risk reduction among initiates into intravenous drug use 1982-1987. Am. J. Drug Alcohol Abuse 17:39-48.[Medline]
    244. 244
  244. Wagner, F., R. Fink, R. Hart, C. Lersch, H. Dancygier, and M. Classen. 1992. Ethanol inhibits interferon-gamma secretion by human peripheral lymphocytes. J. Stud. Alcohol 53:277-280.[Medline]
    245. 245
  245. Waltenbaugh, C., and J. D. Peterson. 1997. Ethanol impairs the induction of delayed hypersensitivity in C57BL/6 mice. Alcohol 14:149-153.[CrossRef][Medline]
    246. 246
  246. Waltenbaugh, C., K. Vasquez, and J. D. Peterson. 1998. Alcohol consumption alters antigen-specific Th1 responses: mechanisms of deficit and repair. Alcohol Clin. Exp. Res. 22:220S-223S.
    247. 247
  247. Wang, J. Y., B. Liang, and R. R. Watson. 1997. Alcohol consumption alters cytokine release during murine AIDS. Alcohol 14:155-159.[CrossRef][Medline]
    248. 248
  248. Wang, Y., D. S. Huang, P. T. Giger, and R. R. Watson. 1993. Ethanol-induced modulation of cytokine production by splenocytes during murine retrovirus infection causing murine AIDS. Alcohol Clin. Exp. Res. 17:1035-1039.[Medline]
    249. 249
  249. Wang, Y., D. S. Huang, P. T. Giger, and R. R. Watson. 1994. Influence of chronic dietary ethanol on cytokine production by murine splenocytes and thymocytes. Alcohol Clin. Exp. Res. 18:64-70.[CrossRef][Medline]
    250. 250
  250. Wang, Y., D. S. Huang, and R. R. Watson. 1994. In vivo and in vitro cocaine modulation on production of cytokines in C57BL/6 mice. Life Sci. 54:401-411.[CrossRef][Medline]
    251. 251
  251. Wang, Y., and R. R. Watson. 1994. Chronic ethanol consumption before retrovirus infection is a cofactor in the development of immune dysfunction during murine AIDS. Alcohol Clin. Exp. Res. 18:976-981.[CrossRef][Medline]
    252. 252
  252. Wang, Y., and R. R. Watson. 1994. Chronic ethanol consumption prior to retrovirus infection alters cytokine production by thymocytes during murine AIDS. Alcohol 11:361-365.[CrossRef][Medline]
    253. 253
  253. Watson, E. S., J. C. Murphy, H. N. ElSohly, M. A. Elsohly, and C. E. Turner. 1983. Effects of the administration of coca alkaloids on the primary immune responses of mice: interaction with delta 9-tetrahydrocannabinol and ethanol. Toxicol. Appl. Pharmacol. 71:1-13.[CrossRef][Medline]
    254. 254
  254. Watzl, B., G. Chen, P. Scuderi, S. Pirozhkov, and R. R. Watson. 1992. Cocaine- induced suppression of interferon-{gamma} secretion in leukocytes from young and old C57BL/6 mice. Int. J. Immunopharmacol. 14:1125-1231.[CrossRef][Medline]
    255. 255
  255. Watzl, B., P. Scuderi, and R. R. Watson. 1991. Influence of marijuana components (THC and CBD) on human mononuclear cell cytokine secretion in vitro. Adv. Exp. Med. Biol. 288:63-70.[Medline]
    256. 256
  256. Weber, R., B. Ledergerber, M. Opravil, W. Siegenthaler, and R. Luthy. 1990. Progression of HIV infection in misusers of injected drugs who stop injecting or follow a programme of maintenance treatment with methadone. Br. Med. J. 301:1362-1365.
    257. 257
  257. Weber, R. J., L. C. Band, B. deCosta, A. Pert, and K. C. Rice. 1991. Neural control of immune function: opioids, opioid receptors and immunosuppression. NIDA Res. Monogr. 105:96-102.
    258. 258
  258. Weber, R. J., and A. Pert. 1989. The periaqueductal gray matter mediates opiate-induced immunosuppression. Science 245:188-190.[Abstract/Free Full Text]
    259. 259
  259. Wetzel, M. A., A. D. Steele, T. K. Eisenstein, M. W. Adler, E. E. Henderson, and T. J. Rogers. 2000. Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-{gamma}-inducible protein-10 expression in human peripheral blood mononuclear cells. J. Immunol. 165:6519-6524.[Abstract/Free Full Text]
    260. 260
  260. Whipham, T. 1875. Fatal pleuropneumonia in the case of a man aged 56, addicted to the abuse of morphia, alcohol and bromide of potassium. Trans. Clin. Soc. Lond. 8:108.
    261. 261
  261. Wilson, R. I., and R. A. Nicoll. 2002. Endocannabinoid signaling in the brain. Science 296:678-682.[Abstract/Free Full Text]
    262. 262
  262. Xu, W., T. Flick, J. Mitchel, C. Knowles, and K. Ault. 1999. Cocaine effects on immunocompetent cells: an observation of in vitro cocaine exposure. Int. J. Immunopharmacol. 21:463-472.[CrossRef][Medline]
    263. 263
  263. Yamamoto, Y., T. W. Klein, and H. Friedman. 1993. Differential effects of ethanol on permissive versus nonpermissive macrophages infected with Legionella pneumophila. Proc. Soc. Exp. Biol. Med. 203:323-327.[CrossRef][Medline]
    264. 264
  264. Yates, S. L., M. Bencherif, E. N. Fluhler, and P. M. Lippiello. 1995. Up-regulation of nicotinic acetylcholine receptors following chronic exposure of rats to mainstream cigarette smoke or alpha 4 beta 2 receptors to nicotine. Biochem. Pharmacol. 50:2001-2008.[CrossRef][Medline]
    265. 265
  265. Yeager, M. P., T. A. Colacchio, C. T. Yu, L. Hildebrandt, A. L. Howell, J. Weiss, and P. M. Guyre. 1995. Morphine inhibits spontaneous and cytokine-enhanced natural killer cell cytotoxicity in volunteers. Anesthesiology 83:500-508.[CrossRef][Medline]
    266. 266
  266. Zhang, P., G. J. Bagby, D. M. Boe, Q. Zhong, P. Schwarzenberger, J. K. Kolls, W. R. Summer, and S. Nelson. 2002. Acute alcohol intoxication suppresses the CXC chemokine response during endotoxemia. Alcohol Clin. Exp. Res. 26:65-73.[Medline]
    267. 267
  267. Zhang, Z., J. Cork, P. Ye, D. Lei, P. O. Schwarzenberger, W. R. Summer, J. E. Shellito, S. Nelson, and J. K. Kolls. 2000. Inhibition of TNF-{alpha} processing and TACE-mediated ectodomain shedding by ethanol. J. Leukoc. Biol. 67:856-862.[Abstract]
    268. 268
  268. Zhu, L. X., S. Sharma, M. Stolina, B. Gardner, M. D. Roth, D. P. Tashkin, and S. M. Dubinett. 2000. {Delta}-9-Tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J. Immunol. 165:373-380.[Abstract/Free Full Text]
    269. 269
  269. Zhu, W., H. Friedman, and T. W. Klein. 1998. {Delta}9-Tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1. J. Pharmacol. Exp. Ther. 286:1103-1109.[Abstract/Free Full Text]
    270. 270
  270. Zhu, W., T. Igarashi, H. Friedman, and T. W. Klein. 1995. {Delta}9-Tetrahydrocannabinol (THC) causes the variable expression of IL2 receptor subunits. J. Pharmacol. Exp. Ther. 274:1001-1007.[Abstract/Free Full Text]
    271. 271
  271. Zhu, W., T. Igarashi, Z.-T. Qi, C. Newton, R. E. Widen, H. Friedman, and T. W. Klein. 1993. Delta-9-tetrahydrocannabinol (THC) decreases the number of high and intermediate affinity IL-2 receptors of the IL-2 dependent cell line NKB61A2. Int. J. Immunopharmacol. 15:401-408.[Medline]

Clinical Microbiology Reviews, April 2003, p. 209-219, Vol. 16, No. 2
0893-8512/03/$08.00+0     DOI: 10.1128/CMR.16.2.209-219.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jamali, A., Mahdavi, M., Hassan, Z. M., Sabahi, F., Farsani, M. J., Bamdad, T., Soleimanjahi, H., Motazakker, M., Shahabi, S. (2009). A novel adjuvant, the general opioid antagonist naloxone, elicits a robust cellular immune response for a DNA vaccine. Int Immunol 21: 217-225 [Abstract] [Full Text]  
  • Oeltmann, J. E., Kammerer, J. S., Pevzner, E. S., Moonan, P. K. (2009). Tuberculosis and Substance Abuse in the United States, 1997-2006. Arch Intern Med 169: 189-197 [Abstract] [Full Text]  
  • Kelschenbach, J., Ninkovic, J., Wang, J., Krishnan, A., Charboneau, R., Barke, R. A., Roy, S. (2008). Morphine Withdrawal Inhibits IL-12 Induction in a Macrophage Cell Line through a Mechanism That Involves cAMP. J. Immunol. 180: 3670-3679 [Abstract] [Full Text]  
  • Chang, S. L., Beltran, J. A., Swarup, S. (2007). Expression of the Mu Opioid Receptor in the Human Immunodeficiency Virus Type 1 Transgenic Rat Model. J. Virol. 81: 8406-8411 [Abstract] [Full Text]  
  • Wang, J., Barke, R. A., Roy, S. (2007). Transcriptional and Epigenetic Regulation of Interleukin-2 Gene in Activated T Cells by Morphine. J. Biol. Chem. 282: 7164-7171 [Abstract] [Full Text]  
  • Irwin, M. R., Olmos, L., Wang, M., Valladares, E. M., Motivala, S. J., Fong, T., Newton, T., Butch, A., Olmstead, R., Cole, S. W. (2007). Cocaine Dependence and Acute Cocaine Induce Decreases of Monocyte Proinflammatory Cytokine Expression across the Diurnal Period: Autonomic Mechanisms. J. Pharmacol. Exp. Ther. 320: 507-515 [Abstract] [Full Text]  
  • Feng, P., Truant, A. L., Meissler, J. J. Jr., Gaughan, J. P., Adler, M. W., Eisenstein, T. K. (2006). Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to Oral Salmonella enterica Serovar Typhimurium Infection. Infect. Immun. 74: 5221-5226 [Abstract] [Full Text]  
  • Feng, P., Wilson, Q. M., Meissler, J. J. Jr, Adler, M. W., Eisenstein, T. K. (2005). Increased Sensitivity to Salmonella enterica Serovar Typhimurium Infection in Mice Undergoing Withdrawal from Morphine Is Associated with Suppression of Interleukin-12. Infect. Immun. 73: 7953-7959 [Abstract] [Full Text]  
  • Roy, S., Wang, J., Charboneau, R., Loh, H. H., Barke, R. A. (2005). Morphine Induces CD4+ T Cell IL-4 Expression through an Adenylyl Cyclase Mechanism Independent of the Protein Kinase A Pathway. J. Immunol. 175: 6361-6367 [Abstract] [Full Text]  
  • Wang, J., Barke, R. A., Charboneau, R., Roy, S. (2005). Morphine Impairs Host Innate Immune Response and Increases Susceptibility to Streptococcus pneumoniae Lung Infection. J. Immunol. 174: 426-434 [Abstract] [Full Text]  
  • Gekker, G., Hu, S., Wentland, M. P., Bidlack, J. M., Lokensgard, J. R., Peterson, P. K. (2004). {kappa}-Opioid Receptor Ligands Inhibit Cocaine-Induced HIV-1 Expression in Microglial Cells. J. Pharmacol. Exp. Ther. 309: 600-606 [Abstract] [Full Text]  
  • EL-Gohary, M., Eid, M. A (2004). Effect of cannabinoid ingestion (in the form of bhang) on the immune system of high school and university students. Hum Exp Toxicol 23: 149-156 [Abstract]  
  • Arjona, A., Boyadjieva, N., Sarkar, D. K. (2004). Circadian Rhythms of Granzyme B, Perforin, IFN-{gamma}, and NK Cell Cytolytic Activity in the Spleen: Effects of Chronic Ethanol. J. Immunol. 172: 2811-2817 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Friedman, H.
Right arrow Articles by Klein, T. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Friedman, H.
Right arrow Articles by Klein, T. W.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»